Whennonvolatileacidisaddedtobodyfluids,asindiabetic ketoacidosis,the[H+]increases(pHdecreases),andthe[HCO3−]decreases.Inadditiontheconcentrationoftheanionassociatedwiththenonvolatileacidincreases.Thischangeinanionconcentrationprovidesaconvenientwayofanalyzingthecauseofametabolicacidosisbycalculatingwhatistermedtheanion gap. TheaniongaprepresentsthedifferencebetweentheconcentrationofthemajorECFcation(Na+)andthemajorECFanions(Cl− andHCO3−):
Undernormalconditionstheaniongaprangesfrom8to16mEq/L.Itisimportanttorecognizethatananiongapdoesnotactuallyexist.Allcationsarebalancedbyanions.Thegapsimplyreflectstheparametersthataremeasured.Inreality:
IftheanionofthenonvolatileacidisCl− ,theaniongapwillbenormal(i.e.,thedecreasein[HCO3−]ismatchedbyanincreasein[Cl−]).Metabolicacidosisassociatedwithdiarrheaorrenaltubularacidosis(i.e.,defectinrenalH+ secretion)hasanormalaniongap.Incontrast,iftheanionofthenonvolatileacidisnotCl− (e.g.,lactate,β-hydroxybutyrate),theaniongapwillincrease(i.e.,thedecreasein[HCO3−]isnotmatchedbyanincreasein[Cl−]butratherbyanincreaseintheconcentrationoftheunmeasuredanion).Theaniongapisincreasedinmetabolicacidosis–associatedketoacidosis(e.g.,diabetesmellitus)withrenalfailure,lacticacidosis,oringestionoftoxinsorcertaindrugs(e.g.,largequantitiesofaspirin).Thuscalculationoftheaniongapisausefulwayofidentifyingtheetiologyofmetabolicacidosisintheclinicalsetting.
Albuminisanegativelychargedmacromolecule,anditmakesaconsiderablecontributionto“unmeasuredanions.”Asaresulttheaniongapmustbeadjustedinpatientswhohaveanabnormalserum[albumin].Foreach1g/dLchangeinserum[albumin],theaniongapneedstobeadjustedinthesamedirectionby2.5mEq/L.
ICF. The increase in the pH inhibits the respiratory centers, which reduces the ventilatory rate, thus the PCO2 is elevated (respiratory compensation).
The renal compensatory response to metabolic alkalosis is to increase excretion of HCO3 − by reducing its reabsorption along the nephron. Normally this occurs quite rapidly (minutes to hours) and effectively. Enhanced renal excretion of HCO3 − eventually returns the pH and [HCO3 −] to normal, provided the underlying cause of the initial acid-base disturbance is corrected. When the pH is corrected, the ventilatory rate also returns to normal.